Immobility

Surgical anaesthesia usually requires hypnosis, antinociception (ensuring blood pressure and heart rate control) and immobility with varying degrees of muscle relaxation. However, the relative contribution of these three components to the state of anaesthesia may vary between different anaesthesias and surgical procedures. While volatile anaesthetics may be used to produce anaesthesia in and by themselves, most often anaesthesia is produced by a combination of drugs. Anaesthesia produced by the concomitant use of hypnotics, analgesics and neuromuscular blocking drugs is called ‘balanced anaesthesia’.Surgical anaesthesia usually requires hypnosis, antinociception (ensuring blood pressure and heart rate control) and immobility with varying degrees of muscle relaxation. However, the relative contribution of these three components to the state of anaesthesia may vary between different anaesthesias and surgical procedures. While volatile anaesthetics may be used to produce anaesthesia in and by themselves, most often anaesthesia is produced by a combination of drugs. Anaesthesia produced by the concomitant use of hypnotics, analgesics and neuromuscular blocking drugs is called ‘balanced anaesthesia’. © Pedro L. Gambús and Jan F.A. Hendrickx 2020.Peer reviewe

Population pharmacokinetic modelling of intravenous paracetamol in fit older people displays extensive unexplained variability.

as target for effective analgesia.A population PK-analysis, using NONMEM 7.2, was performed based on 601 concentrations of paracetamol from 30 fit older people (median age 77.3 years, range [61.8-88.5], body weight 79 kg [60-107]). All had received an IV paracetamol dose of 1000 mg (over 15 min) after elective knee surgery. , respectively, in 90% of the population and above 15.5 and 11.7, respectively, in 10% at these dosing regimens.The target concentration was achieved in the average patient with 1000 mg every 6 h, while every 8 h resulted in underdosing for the majority of the population. Furthermore, due to a large (unexplained) interindividual variability in paracetamol PK a relevant proportion of the fit older people remained either under- or over exposed.AIMSMETHODSRESULTSCONCLUSIONSPharmacolog

Rapacuronium 2.0 or 2.5 mg kg(-1) for rapid-sequence induction: comparison with succinylcholine 1.0 mg kg(-1)

The purpose of this nine-centre study in 602 patients was to show that the frequency of acceptable intubating conditions after rapacuronium 2.0 or 2.5 mg kg(-1) is not more than 10% lower than the frequency after succinylcholine 1.0 mg kg(-1) during rapid-sequence induction of anaesthesia with fentanyl 1-2 mug kg(-1) and thiopental 2-7 mg kg(-1). Laryngoscopy and intubation were carried out 60 s after administration of muscle relaxant by an anaesthetist blinded to its identity. Intubating conditions were clinically acceptable (excellent or good) in 91.8% of patients given succinylcholine and in 84.1 and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg(-1) respectively. With respect to the percentage of clinically acceptable intubating conditions, the estimated difference (and the upper limit of the one-sided 97.5% confidence interval) between succinylcholine and rapacuronium 2.0 mg kg(-1) was 7.8 (14.4)% and between succinylcholine and rapacuronium 2.5 mg kg(-1) it was 4.0 (10.2)%. For both comparisons, the upper limit of the one-sided confidence interval exceeded the predefined 10% difference. Hence, it could not be demonstrated that the intubating conditions with either of the two doses of rapacuronium were not inferior to those with succinylcholine 1.0 mg kg(-1). The increase in heart rate was significantly greater during the first 5 min in the rapacuronium groups, but the arterial pressure increased significantly only in the succinylcholine group (P<0.001). Respiratory side-effects were observed in 4.0, 13.5 and 18.5% of patients after succinylcholine and rapacuronium 2.0 and 2.5 mg kg(-1) respectively (P<0.05). As the non-inferiority of intubating conditions after rapacuronium 2.0 and 2.5 mg kg(-1) could not be proven, succinylcholine should be considered the neuromuscular blocking agent that provides better intubating conditions for rapid-sequence induction